DIABETES OVERVIEW AND UPDATE

1. DIABETES OVERVIEW AND UPDATE Barb Bancroft, RN, MSN, PNP BBancr9271@aol.com www.barbbancroft.com

2. Historical highlights…in the old days… • Diabetes—”to siphon” • Mellitus—”sweet” • Nurse… • “Taste thy patient’s urine, for if it be sweet…” ---Dr. Thomas Willis

3. When I was in Nursing School…it was called “sugar diabetes”…the evolution of the name… Juvenile Onset Diabetes Mellitus (JODM) Adult Onset Diabetes Mellitus (AODM) Insulin Dependent Diabetes Mellitus (IDDM) Non-insulin Dependent Diabetes Mellitus (NIDDM) Type I (Roman numeral used) Type II (Roman numeral used) Type 1 (Arabic number) Type 2 (Arabic number)

4. Definition of Diabetes Mellitus • Chronic disorder of carbohydrate, lipid, and protein metabolism characterized in its fully expressed clinical form by an absolutedeficiency of insulin (Type 1 diabetes) or a relative insulin deficiency (Type 2 diabetes). • Huh? • Type 1—no insulin • Type 2—insulin resistance • PLUS…it’s a PROthrombotic, PROinflammatory, and PROatherosclerotic disease! So be PRO-active in DX and RX! • Is this a cardiovascular disease?

5. Type 2 diabetes—the numbers • 1.5 million new cases diagnosed per year in the U.S. • Over 20 years of age: 20.8 million Americans (9.6%); 1/3 have no clue • Over 60 years of age: 10.3 million or 20.9% of all people • Usual onset after 40; 70% increase in incidence under 40 in last decade • Under 20 years of age: 176,500 or 0.22% of the population; 1 in every 400-600 kids with Type 1 • 2 million adoloescents (1 in 6 overweight adolescents) aged 12-19 have prediabetes • 50% of all new cases of Pediatric diabetes are TYPE 2…not Type 1…

6. Who’s at risk? Who’s sitting in YOUR waiting room? • Genetic risk for Type 1 and for Type 2 diabetes—family history, sibling or parent • How many genes?

7. Family history • Family history of early coronary artery disease • What is meant by early?

8. Hypertension • Greater than 140/90 increases the risk of diabetes • 50-60% of newly diagnosed patients also have HTN at diagnosis • An interesting note: A family history of hypertension in a child with Type 1 diabetes increases their risk of developing nephropathy

9. High risk ethnic groups • African American • Native American • Asian American • Hispanic American • Pacific Islander • Indian (from India)

10. Impaired glucose tolerance • Gestational diabetes • Baby weighing greater than 9 lbs. • Were YOU, as a baby, exposed to hyperglycemia en utero?

11. Type 2 diabetes risk factors • Weight gain

12. What did you weigh as a kid? The odds that a person who is normal weight at age 18 will develop diabetes later in life are 1-in-5 or 1-in-6. However, if a child is very obese at age 18, they have a 3-in-4 chance of developing diabetes. The lifetime risk of developing diabetes, based on a body mass index at age 18, is as follows:

13. BMI and risk of Type 2 (T2)diabetes • A BMI under 25 (normal BMI)—risk of T2 diabetes for women is 17%; risk of diabetes for men is 20% • A BMI between 25-29—risk of T2 diabetes for women is 35%; risk of diabetes for men is 30% • A BMI between 30-34—risk of T2 diabetes for women is 55%; risk of diabetes for men is 57% • A BMI greater than 35—risk of T2 diabetes for women is 74%; risk of diabetes for men is 70% (CDC—Diabetes Branch, May 2006)(June 2006, ADA)

14. Within a single ethnic group… • Diet (high calorie, high fat) • Lifestyle (Lack of physical activity and sedentary lifestyle) • Both play a major role in obesity and insulin resistance with DM

15. Abdominal obesity as a risk factor • Abdominal obesity and insulin resistance • Visceral fat is an endocrine organ and is metabolically active • It is insulin resistant • Produces inflammatory mediators such as TNF-α and IL-6, • Waist greater than 38 inches in females increases the risk by 6-fold • What should we look like?

16. Other conditions that increase the risk of Type 2 diabetes—PCOS and documented hypoglycemia • Polycystic ovary syndrome (PCOS) • Polycystic ovary syndrome (PCOS)—5-10% of women of reproductive age; increasing at the same rate as Type 2 DM and metabolic syndrome in U.S. • Anovulation, irregular menses, androgen excess, insulin resistance, increased CV risk and Type 2 DM • Rx: Metformin and “glitazones” decrease insulin resistance: WORD TO THE WISE: These oral drugs also decrease the efficacy of COCs and increase ovulation—need 2 forms of birth control unless pregnancy is the goal • History of hypoglycemia (documented with OGTT)

17. Undesirable lipid levels • HDL less than 35 mg/dL • Triglycerides greater than 150 mg/dL • Think diabetes or hypothyroidism with the above lipid profile • Draw a FBS and a TSH

18. Type 1 diabetes • Type 1 DM—primarily diagnosed in pre-teens or teenagers; onset prior to age 40 in the majority of patients; • Caucasians greater than African-Americans • Finland #1 country in world with Type 1 DM • 1 in 150 kids by the age of 15

19. Type 1 Diabetes • Associated with immune response genes and HLA-DR3 and HLA-DR4 • Autoimmune attack against specific components of the islet beta cellsof the pancreas (anti-glutamic acid decarboxylase antibodies—anti-GAD; anti-islet cell antibodies) • Usually present with 3 p’s (loss—polyuria, polydipsia, polyphagia), and weight loss • Classic presentation is in a Caucasian, blue-eyed, blonde-haired kid

20. Type 1 diabetes • What triggers the autoimmune response? • The most likely culprit is one of the childhood viruses… • Coxsackie B? Measles? Influenza A or B?

21. Other conditions associated with Type 1 diabetes • Autoimmune diseases are more common • Celiac disease • Thyroid disease • Pernicious anemia

22. Secondary diabetes • Exocrine pancreatic disease—cystic fibrosis • Cushing’s disease or syndrome • Drugs—corticosteroids, L-dopa, beta-blockers, atypical anti-psychotics (especially Clozapine/Clozaril and Olanzapine/Zyprexa), sympathomimetics, niacin, glucosamine, thiazide diuretics • Hospital critical care--stress

23. Hyperglycemia in the hospital setting… • Inpatient hyperglycemia in people with or without diabetes is associated with an increased risk of complications and mortality, a longer hospital stay, a higher admission rate to the ICU, and higher hospitalization costs • Control is challenging…what is the best way to control hyperglycemia in the hospital setting? • Basal/bolus therapy is more efficient than sliding scale which is associated with poorer glycemic control and an increase risk of hypoglycemia (Umpierrez GE, Palacio A, Smiley D. Sliding Scale Insulin Use: Myth or Insanity? The Am J of Med 2007 (July): 120 (7).

24. Laboratory Tests • Prediabetes…one-step away… HUH? • 54 million Americans with prediabetes • Asymptomatic fasting blood sugars between 100 mg/dL and 125 mg/dL • Used to be called impaired glucose tolerance • May have metabolic syndrome

25. Central obesity and the metabolic syndrome (insulin resistance syndrome) • What is the metabolic syndrome? (Previously known as syndrome X) • A clustering of risk factors that, in the aggregate, sharply increase the risk of cardiovascular disease and diabetes • By the time a diagnosis of diabetes is made, 70-90% of patients have metabolic syndrome, irrespective of ethnicity or the definition used • 1 million adolescents have metabolic syndrome • What is the definition of metabolic syndrome?

26. Definition varies by group: NCEP ATP III guidelines: Metabolic syndrome or IRS (insulin resistance syndrome) • Central obesity—waist size greater than 40.2 inches in men, 34.6 inches in women • High TG (>150 mg/dL), • Low HDL (less than 40 mg/dL in men, less than 50 mg/dL in women) • Hypertension (≥ 130/85 mm Hg) • Fasting glucose ≥ 110 mg/dL (or greater than 100 mg/dL) • Metabolic syndrome is present when any 3 of these risk factors are present • PCOS (polycystic ovary syndrome is a form of metabolic syndrome/IRS)

27. Laboratory diagnosis • Fasting plasma glucose—after 8 hours without caloric intake • A.M. specimens greater than or = to 126 mg/dL (previous was 140 mg/dL)

28. Or… • Random glucose of greater than or equal to 200 mg/dL • Postprandial glucose excursions with subsequent hypoglycemia—patient with early diabetes can present with this picture—give glucometer to take home and measure • Postprandial glucose excursions are also associated with an increased risk of CV disease…

29. Laboratory diagnosis • Hemoglobin A1C—gold standard for measuring long-term glycemic control—how does it work? RBC life span • 50% of glycosylated hemoglobin is from previous month; 25% from the month before; 25% 3-4 months ago • Normal range is 4-6%; each percent equals 20-22 mg/dL of plasma glucose (6% is TOO HIGH—but is considered normal range by laboratory) • HbA1C of 4% is the equivalent of a FPG of 80-88 mg/dL; 10% = 200-220 mg/dL • What does the ADA recommend for HbA1C for adults? (Less than 7) Clinical endocrinologists for adults? (Less than 6.5)

30. Hemoglobin A1c for kids (ADA guidelines) • Guidelines for kids—less than 8.5 but greater than 7.5 for toddlers and preschoolers 0-6 years of age • Less than 8 for kids 6-12 • Less than 7.5 for adolescents and young adults (13-19) • More liberal numbers for kids and developing brains who are more vulnerable to the effects of hypoglycemia and who may not be able to effectively recognize or speak about the symptoms of hypoglycemia • The DCCT data certainly showed that tighter blood glucose controls increase the risk of serious hypoglycemia BUT also decrease the risk of long-term complications

31. Hemoglobin A1C for older adults • More complex because of co-morbidities (example aggressive control of BP + BS may increase the risk of falls) • How aggressive should we be? • LIGHT mnemonic is useful • L—life expectancy: estimate average life expectancy based on age and health status • I—impact of geriatric syndromes and other co-morbidities • G—goals of care and patient preferences • H—help the patient prioritize and develop a care plan • T—Time required to benefit from the therapeutic intervention

32. Six syndromes to consider in older patients with diabetes • Polypharmacy—drug burden and drug-drug and drug-disease interactions are very common • Depression—increased prevalence and incidence; interferes with self-management • Cognitive impairment—screen yearly and more often in patients having difficulty with disease management and self-care (check TSH and B12); is dementia more common in diabetics?

33. Six syndromes to consider in older patients with diabetes • Urinary incontinence—from glucosuria, neurogenic bladder, stool impaction, UTI, vaginal yeast infection • Falls— • Undertreated pain—may not mention or may just blame it on normal aging; may not describe neuropathic pain in the usual terms of tingling, burning, but use terms such as aching, discomfort

34. Basic physiology/pathophysiology • Insulin is a growth hormone—stores fat and sugar and stimulates protein synthesis after the meal • Too much? WEIGHT GAIN; hypoglycemia • Glucagon is a catabolic hormone produced during the fasting state; breaks down stored glycogen • Too much? WEIGHT LOSS; hyperglycemia

35. The fasting state • The pancreas produces glucagon for glycogenolysis (break down stored sugar in the liver) to maintain a steady state of blood glucose • Lipolysis—breaks down fat tissue and forms free fatty acids • Gluconeogenesis—turns proteins into sugar • Type 1 ketoacidosis is a prolonged fasting state; absolute deficiency of insulin; glucagon is working overtime; weight loss; glycogenolysis and lipolysis with hyperglycemia and fatty acid release (ketones); ketones and glycosuria cause a significant osmotic diuresis (significant dehydration)

36. Symptoms of DKA (Diabetic Ketoacidosis) • Dehydration • Abdominal pain • Anorexia, weight loss • Kussmaul’s respirations (acidosis) • Tachycardia • Weakness, fatigue • Fruity breath odor • hypotension • N and/or V • Confusion, decreased reflexes, coma

37. Treatment of DKA • Dehydration is your first priority • GIVE FLUIDS…what kind? • Then what? Regular insulin IV • Then what? Check electrolytes and bicarb

38. Pathophysiology of Type 2 DM • Early in the disease—insulin resistance is characterized by a subnormal receptor response to insulin (partially due to abdominal obesity) • Abnormal beta cell response with an abnormal release of insulin to glucose—too much released resulting in hyperinsulinemia and hypoglycemia in the postprandial state • What are the consequences of hyperinsulinemia?

39. Hyperinsulinemia… • Increased TG and decreased HDLs • Sodium and water retention—HTN • Stimulate fat storage (CHO to fats) • Prothrombotic • Proinflammatory • Triggers endothelial cell dysfunction • YIKES!!

40. Type 2 diabetes • Metabolic derangements aren’t usually as severe as Type 1; as insulin resistance continues, serum glucose levels gradually increase; with increasing glucose levels the pancreas responds by increasing insulin output resulting in hyperinsulinemia • Few symptoms initially, 2 P’s (no polyphagia), weight gain due to hyperinsulinemia • Other symptoms—fatigue, diplopia, nocturia • Skin infections, vaginal infections, poor wound healing, neuropathy • Cardiovascular complications may be the first presenting symptoms—MI, PAD, Stroke • “Silent” for a full decade in some individuals

41. Some new physiology… • You eat a meal…and then? • The intestine releases incretin hormones known as GLP-1 (glucagon-like peptide 1) and GIP (glucose-dependent insulinotropic polypeptide) throughout the day, with an increase right after the meal (postprandial increase) • The incretin hormones influence the pancreas to increase the synthesis and release of insulin and decrease the synthesis and release of glucagon • Drugs that affect incretin—Exenatide (Byetta); symlin (Amlin); sitagliptin (Januvia)

42. And then what? • Insulin acts on insulin receptors in the liver, skeletal muscle tissue and adipose tissue to trigger the entry of sugar into the cells • (Obesity decreases the number of insulin receptors; exercise increases the receptor sensitivity)—HENCE, the strong recommendation to LOSE weight and exercise! • The liver stores extra glucose as glycogen and releases it as necessary to keep the blood sugar levels in the normal range throughout the day and night • The liver does most of its work at night • Clinical implications of giving metformin at night (Metformin blocks the breakdown of glycogen to glucose)—the whole dose

43. How do you treat it? The usual suspects…(oral drugs) • By decreasing the production of glucose by the liver—Metformin (glucophage) • By increasing insulin sensitivity in the tissues (the glitazones—rosi- and pio-)—Avandia and Actos; metformin (glucophage) • By increasing insulin secretion from the pancreas and increasing insulin receptor sensitivity (the oral sulfonylureas) • By giving oral drugs that reduce postprandial excursions of glucose (repaglinide/Prandin, nateglinide/Starlix) • By inhibiting enzymes in the intestine responsible for breaking down incretins that potentiate insulin release (sitagliptin/Januvia) • By mimicking hormones (incretins) that trigger insulin release from the pancreas (exenatide/Byetta)

44. Oral Drugs…the #1 bestseller • Metformin (glucophage) does not have any direct effect on insulin release from the pancreas—doesn’t require insulin to work • Primary action: DECREASE hepatic glucose production; also, decreases glucose absorption via the GI tract, and may increase sensitivity of insulin receptors • Problem? GI blues, need functioning organs--kidneys and heart especially (check serum creatinine before starting metformin) • Se Creatinine--Cut-off is 1.4 in females and 1.5 in males • Other benefits: lowers BP, increases HDL, lowers LDL • B12 deficiency—longer the use and the higher the dose, the greater the risk

45. Digression: the importance of B12 • B12 is necessary for the healthy production of RBCs and for the maintenance of the central and peripheral nervous system (cognitive function in the CNS and normal PNS function) • B12 deficiency is the one of the top 3 causes of peripheral neuropathy in the U.S. and the #1 cause of nutritional dementia in the U.S. • B12 is stored in the liver for 5 years or so • 39% of the population over 50 has a B12 deficiency • PPIs and Metformin decrease B12 • B12 and peripheral neuropathy in the diabetic • Supplements? How much? • Can you overdose on B12? The one dreaded side effect is…

46. Oral drugs for type 2 DM… • The “Glitazone” sisters—rosi (Avandia), pio (Actos) • Improve muscle receptor sensitivity to insulin with secondary effects in the liver • May slow down the progression of the disease** • Problem? Volume expansion, heart failure, dilutional anemia, weight gain (peripheral, not central) • Good news? Reduce triglycerides • The bad news? Do these drugs increase the risk of cardiovascular events? • Can you use this class of drugs in the patient with heart failure?

47. OLD Drugs…are these even worth using anymore? Considered third-line therapy… • Oral sulfonylureas—Glipizide (Glucotrol) and glyburide (Diabeta, Micronase, Glynase) and glimipiride (Amaryl)… • Increase the secretion of insulin from the pancreas and increase receptor sensitivity • Problem? Weight gain, hypoglycemia, increased cardiovascular risk) (highest doses increased risk vs. metformin; may prevent heart from recovering from brief periods of ischemia) (Canadian Medical Association Journal January 2006) • glimipiride (Amaryl)—safe use in elderly--decreased incidence of hypoglycemia

48. Drug combinations • Glucovance (glyburide and metformin) • Avandamet (rosiglitazone and metformin) • Metaglip (glipizide and metformin) • Actosplus Met (metformin/pioglitazone) • Avandaryl (rosiglitazone/glimepiride) • Duetact (pioglitazone HCl and glimepiride) • Sitagliptin/metformin (Janumet)

49. Other drugs • Repaglinide (Prandin) • Nateglinide (Starlix) • Good for elderly to prevent postprandial excursions • Great if your meals are sporadic

50. Exenatide (Byetta)—incretin mimetic • incretins are responsible for approx. 60% of the post-meal insulin secretion; however, the action of the incretins is impaired in diabetics • Byetta is an incretin mimetic; acts at the GLP-1 receptor in the pancreas that promotes insulin release • Type 2 diabetics who are already receiving metformin, a sulfonylurea, or both and do not have optimal control • Weight loss is a + side effect due to early satiety (10-15 lbs to 40-50 lbs) • Take less than an hour before a.m. and p.m. meals (nausea)